Gene delivery applications

We have investigated the potential of genetically engineered SELP-47K to act as an in situ gel-forming matrix for 

Delivery of Plasmid DNA from Silk-Elastinlike Hydrogels 

DNA release was initially evaluated as a function of polymer concentration, DNA concentration, ionic strength, and 

DNA release was observed for more than 28 days, with apparent intra-gel diffusivities of approximately 10 to 10 ° cm /s, depending on the polymer concentration and cure time (40). Transfection studies performed on encapsulated DNA indicated that it retained in vitro bioactivity equivalent to stock DNA for at least 28 days (50). 

The conformation of plasmid DNA, namely supercoiled, open circular, or linear has been hypothesized to play a role in its transfection efficiency. While conventional thinking has generally indicated a preference for supercoiled DNA, at least one study has shown that the delivery of linear DNA results in prolonged transgene expression in vivo, due to con-catamerization (52). Other studies have shown that the conformation of DNA is irrelevant to the transfection efficiency in vitro and in vivo (53). 

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Son SJ, Bai X, Lee SB (2007a) Inorganic hollow nanoparticles and nanotubes in nanomedicine. Part 1. Drug/gene delivery applications. Drug Discov Today 12 650-656. 

From the structural point of view, polyamines used for gene transfection vary widely in their structures, which range between linear [24, 29-35], branched [12, 30, 32], hyperbranched, and perfect branched dendrimers [36]. In this chapter we present a general overview of the research reported so far using dendritic polyamines in gene delivery applications. Particular focus is made on hyperbranched... 

The search for an efficient and non-toxic gene transfection vector has led to the design and synthesis of a great variety of macromolecular scaffolds. An extensive analysis of the key features for the efficient and safe delivery of genes in vivo and in vitro has led to the conclusion that hyperbranched polymers are potential candidates for further development. In this chapter we have presented a detailed analysis of the different hyperbranched polymer scaffolds commonly used in gene delivery applications. Several structural modifications toward the development of an optimal gene vector have been analyzed. 

Recently, other approaches and modifications of HA for gene delivery applications have been investigated. Among the most interesting ones are mixed chitosan-hyaluronan based gene delivery systems [68-70] and PEG-HA photocrosslinked hydrogels [71]. HA has also been used to improve the biocompatibility of branched PEI via covalent conjugation [72],... 

PEI grafting on chitosan is becoming a popular approach for modification of chitosan for gene delivery applications. In recent years several efforts to develop chitosan-g-PEI delivery vectors have been published. These include incorporation of mannose [117] and folic acid [118] derivatives for targeted delivery and application of chitosan-g-PEI for the delivery of siRNA [119]. 

Safinya CR, Ewert KK, Ahmad A, Evans HM, Raviv U, Needleman DJ, Lin AJ, Slack NL, George CX, Samuel CE (2006) Cationic liposome-DNA complexes from liquid crystal science to gene delivery applications. Phil Transact Royal Soc A 364 2573-2596... 

Boomer JA, Thompson DH (1999) Synthesis of acid-labile diplasmenyl lipids for dmg and gene delivery applications. Chem Phys Lipids 99 145-153... 

As mentioned previously, ELPs can be further customized by combining different pentapeptide blocks, to produce block copolymers with sensitivity to several different temperatures (20,21). Block copolymers are of great interest for drug and gene delivery applications, significantly because of their ability to form micellar structures with the ability to encapsulate drugs or nucleic acids within the core, and to display targeting moieties on the periphery of the shell (29). 

P. Wich, J. Frechet, Degradable dextran particles for gene delivery applications, Aust. J. Chem. 65 (2012) 15. 

Cationic Dendritic Systems as Non-viral Vehicles for Gene Delivery Applications... 

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